Gao
etal. J Nanobiotechnol (2021) 19:96
https://doi.org/10.1186/s12951-021-00825-4
REVIEW
Biomedical applications of2D
monoelemental materials formed bygroup VA
andVIA: aconcise review
Ping Gao
1†
, Yufen Xiao
2†
, YuliangWang
1
, Leijiao Li
1*
, Wenliang Li
3*
and Wei Tao
2
Abstract
The development of two-dimensional (2D) monoelemental nanomaterials (Xenes) for biomedical applications has
generated intensive interest over these years. In this paper, the biomedical applications using Xene-based 2D nano-
materials formed by group VA (e.g., BP, As, Sb, Bi) and VIA (e.g., Se, Te) are elaborated. These 2D Xene-based theranostic
nanoplatforms confer some advantages over conventional nanoparticle-based systems, including better photother-
mal conversion, excellent electrical conductivity, and large surface area. Their versatile and remarkable features allow
their implementation for bioimaging and theranostic purposes. This concise review is focused on the current devel-
opments in 2D Xenes formed by Group VA and VIA, covering the synthetic methods and various biomedical applica-
tions. Lastly, the challenges and future perspectives of 2D Xenes are provided to help us better exploit their excellent
performance and use them in practice.
Keywords: 2D materials, Monoelemental, Group VA and VIA, Biomedical applications
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Background
Two-dimensional (2D) materials are one of the emerg-
ing materials, which have more than 100nm or even sev-
eral microns with one or a few atomic thicknesses [1]. In
2004, Novoselov and Geim adopted the mechanical sepa
-
ration method to obtain graphene [2]. Graphene is a kind
of two-dimensional material with hexagonal honeycomb
shape formed by sp
2
hybridization of carbon protons [3].
Due to its excellent electrical conductivity, high thermal
conduct covering sensors, transistors, new energy bat
-
teries, hydrogen storage materials, aerospace and so on
[46]. e great success of graphene has led to a remark
-
able boom in the development of 2D nanomaterials, such
as transition metal dihalide (TMD), nitrides and car
-
bonitrides (MXenes), hexagonal boron nitride (h-BN),
graphite phase nitrogen carbide (g-C
3
N
4
), molybdenum
disulfide(MoS
2
), layered rare earth hydroxide (LRH), lay-
ered double hydride (LDH) and their derivatives [710].
2D nanomaterials with ultrathin lamellate nanostructure
exhibit weak interlayer bonding and strong covalent in-
plane bonding [11]. ere are multifarious unique prop
-
erties of 2D nanomaterials including the large surface
area, the improved chemical and physical reactivities
[1214]. Particularly, the dramatically increased surface
area of 2D nanomaterials affects a 2D wave function due
to the quantum confinement effects. Consequently, 2D
nanomaterials are characterized by impressive photonic
[15], catalytic [16], magnetic [17], and electronic proper
-
ties [18] that differ from those of the bulk counterparts,
resulting in a wide-ranging application.
In recent years, 2D monoelemental nanomateri
-
als (Xenes) based on group VA and VIA have gradu-
ally entered the researchers’ field of vision, which is
Open Access
Journal of Nanobiotechnology
*Correspondence: lileijiao@cust.edu.cn; wenliangl@ciac.ac.cn
Ping Gao and Yufen Xiao contributed equally to this work
1
School of Chemistry and Environmental Engineering, Changchun
University of Science and Technology, Changchun 130022, China
3
Jilin Collaborative Innovation Center for Antibody Engineering, Jilin
Medical University, Jilin 132013, China
Full list of author information is available at the end of the article
Page 2 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
encouraged by the dramatically development of phos-
phorene (black phosphorus, BP) [1922]. Due to the
excellent optical and electronic properties, Xenes have
been considered to be promising biological theranos
-
tic agents to address various challenges in healthcare
[2330]. Xenes can be used as diagnosis agents for com
-
puted tomography (CT), photoacoustic imaging (PAI),
fluorescence imaging (FI), etc. [3134]. Moreover, Xenes
are employed in disease phototherapy, such as photo
-
thermal therapy (PTT) and photodynamic therapy (PDT)
against tumor, bacteria and virus [3541]. e large sur
-
face area of Xenes endows them an incomparable high
loading capacity of therapeutic and/or fluorescent mole
-
cules compared with traditional nanoparticle-based drug
delivery platforms. Besides, Xenes also could construct
biosensors with the attachment of various biological
markers like DNA, etc. [42, 43]. is paper reviews the
applications of Xenes formed by Group VA and VIA in
biomedical fields. To start with, the synthesis and physi
-
cal–chemical properties of Xenes are introduced. And
then their research progress in biomedicine fields were
summarized such as bioimaging, therapy and antibac
-
terial. Finally, on the basis of summarizing the current
situation, the paper puts forward the challenges and
prospects for future development of Xenes in group VIA
and VA (Fig.1).
Synthesis ofXenes
e synthetic methods of 2D Xenes can be categorized as
top-down fabrication and bottom-up synthesis (Table1).
e top-down method mainly uses mechanical force or
molecular intercalation to destroy interlayer bonding,
so as to strip the block and obtain a single or multi-layer
nanometer sheets [44]. e bottom-up approach is to use
chemical conversion methods to directly react different
molecular precursors to form nanosheets [45, 46].
Top‑down
e top-down method mainly includes solid-phase strip-
ping and liquid-phase stripping. e solid phase stripping
refers to mechanical dissociation stripping. e liquid-
phase stripping relies on ultrasonic exfoliation, electro
-
chemical stripping, plasma-assisted process and so on.
Mechanical cleavage
Mechanical cleavage is an original and basic approach
to strip large layered materials into single or several lay
-
ers of nanometer sheets by mechanical forces using
transparent tape [47]. In recent years, researchers have
Fig. 1 Schematic illustration of the main topics covered in this
review
Table 1 Summary of Xene synthesis method
Periodic
Table
group
Element 2D form Morphology Synthesis methods Refs
VA P Phosphorene Nanosheets and quantum dots Mechanical cleavage, ultrasonic exfoliation,
electrochemical stripping, plasma-
assisted process Other top-down meth-
ods, MBE,CVD, Solvent-thermal method
[4852, 65, 68, 71, 72, 74, 80, 86, 87]
VA As Arsenene Nanosheets and Nanodots Ultrasonic exfoliation, electrochemical
stripping, plasma-assisted process, Other
top-down methods
[55, 62, 69, 73]
VA Sb Antimonene Nanosheets and quantum dots Mechanical cleavage, ultrasonic exfoliation,
electrochemical stripping, plasma-
assisted process, Other top-down meth-
ods, MBE, Vander Waals extension
[26, 50, 56, 67, 70, 73, 75, 89]
VA Bi Bismuthene Nanosheets and quantum dots Ultrasonic exfoliation, Other top-down
methods, MBE, Wet chemistry
[57, 73, 78, 90]
VIA Se Selenene Nanosheets Ultrasonic exfoliation [58]
VIA Te Tellurene Nanosheets and quantum dots Ultrasonic exfoliation, MBE, Solvent-ther-
mal method, thermal evaporation
[59, 79, 88, 91]
Page 3 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
prepared many 2D nanomaterials by this method. In
2014, BP nanoflakes were firstly obtained by repeatedly
peeling the block crystal with transparent tape on Si/
SiO
2
substrate [48, 49]. e BP generated by the method
is easy to oxidize in the environment forming irreversible
phosphorus oxide compounds. erefore, it is necessary
to use inert gas or vacuum in the preparation process
to obtain pure BP nanosheets (Fig. 2a, b). In addition,
submillimeter-sized antimonene is prepared directly on
the SiO
2
/Si substrate by repeatedly tearing a block crys-
tal over the tape. However, the production yield based on
SiO
2
/Si substrate is very low. In 2016, Pablo Ares etal.
developed an improved method with the aid of viscoelas
-
tic polymer on the surface of SiO
2
substrate. As shown
in Fig.2c–h, the results of high resolution transmission
electron microscopy (TEM) and atomic force microscope
Fig. 2 a, b Crystal structure of few-layer phosphorene. a Perspective side view of few-layer phosphorene. b Side and top views of few-layer
phosphorene. Reprinted with permission [48], Copyright 2014 American Chemical Society. ch Antimonene flakes on SiO2 substrates. c Top left,
millimeter-size crystals of antimony. Middle right, adhesive tape with sub-millimeter crystals of antimony. Bottom left, polymer on glass slide with
micrometer antimony flakes. d Optical microscopy image where up to three large flakes of antimony can be seen. e AFM topographic image
showing two flakes of anti-monene located inside the marked region in d. f AFM topography of the 0.2 μm2 antimonene flake inside the blue
square in e showing terraces of different heights. g High-resolution TEM image of a few-layer antimonene flake. The inset is a digital magnification
of the area inside the blue rectangle. h AFM topography acquired on the bilayer terrace marked with a green arrow in f showing atomic periodicity.
Reprinted with permission [50], Copyright 2016 Wiley
Page 4 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
(AFM) proved the excellent stability of antimonene pre-
pared by the improved method. And the theoretical cal-
culations of the antimony monolayer also proved the
inactive character with water and oxygen [50]. Although
mechanical cleavage is an easy and low-cost approach,
the yield is relatively low and the controllability and
repeatability are dissatisfactory.
Ultrasonic exfoliation
Recently, ultrasonic assisted liquid phase stripping has
attracted dramatically increasing attention. e bulk
layered crystal is firstly dispersed in designated medium
such as N-cyclohexyl-2-pyrrolidone (CHP), dimethyl
-
formamide (DMF), dimethylsulfoxide (DMSO), isopro-
pyl alcohol (IPA), N-methyl-pyrrolidone (NMP) and
so on [51]. With the help of ultrasonic wave, abundant
bubbles are generated on the surface of crystal through
hydroxyl radical mediating or pyrolysis reaction dur
-
ing ultrasonic cavitation and thus ultrathin 2D nanoma-
terials are produced finally. High-quality, uniform size,
low-layer BP nanosheets were prepared with ultrasonic
probe by liquid-phase exfoliation in both CHP and NMP
solution under cooling condition (Fig. 3a, b) [52, 53].
Furthermore, Song et al. produced BP quantum dots
(QDs) by liquid-phase exfoliation with ultrasonic probe
in NMP by tuning power and reaction time (Fig.3c) [54].
ese BP QDs possess the average size of 3.5–4.5 nm
and the thickness of 1.2–1.6nm with the lattice fringes
of 0.26nm and 0.32nm assigned to the (004) and (012)
plane of BP. Coincidentally, arsenene (2D arsenic) has
also been prepared using gray arsenic as raw material
by liquid-phase exfoliation in NMP. As shown in Fig.3d,
e, the thickness of the prepared arsenic flakes is 6–12
atomic layers and the size is 100–350nm in average. e
Raman spectra showed thickness dependence. None
-
theless, the products are only arsenic nanoparticles by
replacing solvent medium with toluene when other con
-
ditions are held constant [55]. e lamellar β-antimonene
was obtained by ultrasonication in a mixture of IPA and
water (IPA:water = 4:1) at 400 W for 40 min (Fig. 3f).
e transverse size is greater than 1-3μm
2
accompanied
with the thicknesses 4 nm [56]. Tao et al. synthesized
the ultra-small and uniform size antimony quantum
dots by the two-step combined ultrasonic strategy of
ultrasound probe sonication and ice bath ultrasound in
ethanol, and modified them with 1,2-Distearoyl-sn-glyc
-
ero-3-phosphoethanolamine-N-[methoxy (poly ethylene
glycol)] (DSPE-mPEG) to improve their dispersion and
stability in physiological media. As presented in Fig.3g,
h, the average size of the exposed antimony quantum
dots is approximately 2.8nm, and the average thickness
is approximately 1.6nm. e average size of antimony
quantum dots modified by mPEG is 3.9nm and the aver
-
age thickness is 2.6nm [26].
Ultrathin bismuthene QDs can be produced by liquid-
phase exfoliation in NMP for 48h under the power of
400W (Fig. 3i) [57]. Selenene (2D selenium) has been
experimentally obtained with 200W power liquid-phase
exfoliation along with 360W ultrasound treatment sub
-
sequently. As shown in Fig. 3k, the obtained selenium
nanosheets with the size of 20–130nm and the thickness
of less than 10nm have been successfully applied in pho
-
toelectric fields [58]. Tellurene (2D Tellurium) could also
be obtained by liquid-phase exfoliation in IPA after pul
-
verizing. e prepared 2D Te nanosheets with good sta-
bility keep the crystallization characteristics during the
stripping process (Fig. 3l) [59]. For size/thickness-con
-
trollable preparation of 2D Xenes by ultrasound-assisted
liquid phase exfoliation, the decisive factor should be the
power and the reaction time of ultrasonic. And the first
critical factor should be the appropriate selection of sol
-
vent. e above mentioned organic solvent molecules
could be embedded into the interlayer of layered mate
-
rials like wedges, which is beneficial to break the weak
van der Waals forces and gain ultrathin nano-lamina.
e decisive factor should be the power and the reaction
time of ultrasonicto size/thickness-controllable prepara
-
tion of 2D Xenes [6062]. Ultrasonic exfoliation is one of
Fig. 3 a Basic characterization of exfoliated black phosphorous (CHP as solvent, scale bars 100 μm, 500 nm and 1 nm). Reprinted with permission
[52], Copyright 2015 Macmillan Publishers. a Schematic of solvent exfoliation of BP in NMP solvents via tip ultrasonication and characterization
of solvent-exfoliated BP nanosheets. Reprinted with permission [53], Copyright 2015 American Chemical Society. c Schematic illustration of the
synthesis of BPQDs and experimental morphological (TEM and AFM) images of BPQDs. Reprinted with permission [54], Copyright 2018 Elsevier. d
Schematic of the preparation of arsenenenanosheets in NMP and nanodots in toluene from grey arsenic. Reprinted with permission [55], Copyright
2018 Royal Society of Chemistry. e Experimental morphological (TEM and AFM) images of arsenenenanosheets and nanodots. Reprinted with
permission [55], Copyright 2018 Royal Society of Chemistry. f Experimental morphological (TEM and AFM) images of antimonene, reprinted with
permission [56], Copyright 2016 Wiley. G Fabrication of PEG-coated AMQD. Reprinted with permission, [26] Copyright 2017 Wiley. h Photos of
bulk antimony, antimony powder, AMQDs solution during the preparation, process, TEM and AFM image of AMQDs. Reprinted with permission
[26], Copyright 2017 Wiley. i Fabrication of BiQDs. Reprinted with permission [57], Copyright 2018 American Chemical Society j Experimental
morphological (TEM and AFM) images of BiQDs. Reprinted with permission [57], copyright 2018 American Chemical Society. k Characterizations of
the as-prepared 2D Se through liquid-phase exfoliation. Reprinted with permission [58], Copyright 2019 Elsevier. l Characterization of ultrathin 2D
Tenanosheets. Reprinted with permission [59], Copyright 2018 Wiley
(See figure on next page.)
Page 5 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Page 6 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
the most effective methods for preparing 2D Xenes, and
it is also considered as a universal method for various 2D
Xenes.
Electrochemical stripping
Electrochemical stripping including ion intercalation
method and anodizing method has been used in the syn
-
thesis of graphene. Recently, 2D Xenes were also obtained
with the assistance of mild ultrasound by ion intercala
-
tion method. e embedding cations (such as K
+
, Na
+
,
Li
+
, etc.) could enlarge the space and weaken the van
der Waals force between layers. Besides, these cations
could also react with water to generate hydrogen, which
is beneficial to the separation between layers as well and
thus improves the productivity [63, 64]. For instance, BP
nanosheets were successfully prepared from black phos
-
phorus film by ion intercalation method. As illustrated in
Fig.4a–d, Adriano Ambrosi etal. used black phosphorus
film as anode, platinum plate as cathode, and connected
with copper strip and put it into H
2
SO
4
solution at given
voltage. e solution gradually turned yellow/orange
and finally turned deep orange. After cleaning and vac
-
uum drying, the small particles at the bottom were re-
dispersed in dimethylformamide (DMF). e green/gray
dispersion was obtained by ultrasonic treatment, and BP
nanosheets were obtained after vacuum drying at 40
[65].
e preparation of arsenene (2D arsenic) was achieved
by electrochemical stripping. Bulk arsenic was used as
cathode (working electrode), platinum and Ag/AgNO
3
were used as anode and reference electrode, respec
-
tively. In this reaction, ammonium hexafluorophosphate
(NH
4
PF
4
) was selected as electrolyte and then accumu-
lated on the surface of anode (Fig.4e). e multilayered
arsenic pieces further screen out 2D arsenene with thick
-
ness of 0.6nm. is electrochemical assisted method will
facilitate the application of arsenene in a new genera
-
tion of electronic devices [66]. Using platinum and anti-
mony as electrodes in Na
2
SO
4
and Li
2
SO
4
electrolytes
at 5V for 2h to obtain antimonene (2D antimony) [67].
e voltage polarity and the type of electrolyte have an
important influence on the peeling production (Fig.4f).
Electrochemical stripping is a scalable method to obtain
biocompatible Xenes. Compared with the traditional
method, this method can prepare high yield and low cost
2D materials with high requirements, which have been
realized in phosphorene, MoS
2
and other materials.
Plasma assisted process
is method is important for the fabrication of high-
performance phosphenyl nanoelectronic devices.
Phosphorene could be prepared by pyrolysis of black
phosphorus crystal on SiO
2
/Si substrate using Ar
+
plasma (13.56 MHz RF source), 30 pair pressure and
30 W power at room temperature. According to the
Raman spectra, the frequency of A
2g
mode becomes hard
with the decrease of atomic thickness, while the frequen
-
cies of β
2g
and A
1g
modules are almost constant. is may
be due to the anisotropic structure changes of different
thickness of phosphoranes [68].
Moreover, Tsai et al. synthesized multilayer arse
-
nic nanosheets using plasma-assisted processes on the
InAs substrate (Fig.5a, b) [69]. ere are many factors
that affect the size, thickness and morphology of arse
-
nic nanosheets including annealing time and the plasma
exposure time. e greater the plasma power, the higher
the arsenic phonon mode strength and the more crystal
defects. e heterostructure includes multilayered arse
-
nic, InN and InAs substrates, respectively. e multilayer
antimony nanoribbons can be prepared by immersing the
InSb substrate in a 50–200W N
2
plasma for 30–60min
at 10
1
torr and then drying and annealing in N
2
/H
2
(10/1, V/V) atmosphere for 30–60min (Fig.5c, d) [70].
However, this method is suitable for mass production of
2D nanomaterials due to its high cost and high equip
-
ment requirements.
Other top‑down methods
In addition to the above-mentioned preparation methods
of 2D Xenes, there are many other preparation meth
-
ods. Xu etal. mixed large black phosphorus crystals with
NMP in a 1:1 ratio (weight ratio w/w) under vigorous stir
-
ring by a household mixer for 40min at 250W power to
produce a single layer or several layers of BP nanosheets
[71]. A simple and efficient microwave-assisted liquid-
phase stripping method was performed to prepare BP
nanosheets [72]. A large amount of black phosphorus
was dissolved in a small amount of NMP and heated in
a 600W microwave system at 50°C for 20–40min. And
then the intermediate products were transferred to a
(See figure on next page.)
Fig. 4 a Schematic of the black phosphorus exfoliation procedure. Snapshot of the electrochemical setup with BP flake anode and Pt foil cathode
separated in acidic solution (0.5 M H
2
SO
4
) by a fixed distance of 2 cm at b no potential applied, c after 20 min applying a voltage of + 3 V and d
after 2 h process. A-D Reprinted with permission [65], Copyright 2017 Wiley. e Low-Potential Electrochemical Exfoliation. Scheme. Low-potential
electrochemical exfoliation of native As toward (mono)few-layer arsenene: (blue dots) cations (NH4+); (red dots) anions (PF6). Reprinted with
permission [66], Copyright 2017 Royal Society of Chemistry. f General scheme for the electrochemical exfoliation of layered Sb crystals into 2D
sheets. Reprinted with permission [67], Copyright 2020 Wiley
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Gaoetal. J Nanobiotechnol (2021) 19:96
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Gaoetal. J Nanobiotechnol (2021) 19:96
220W microwave system at 70 for 3min to obtain a
dispersion of stable BP nanosheets. In addition, by using
hepatocholic acid as surfactant, the As, Sb and Bi bulk
crystals were dispersed and stirred acutely in the kitchen
mixer for 2h to obtain 2D As, Sb and Bi nanosheets [73].
TEM images showed that arsenic formed the largest thin
section with folded structure due to its high anisotropy,
and the layered structure was small. e thicknesses of
the synthetic 2D antimony was 10 times less than that
of 2D arsenic. e electronic transfer ability, sensing
performance and electrochemical performance of these
materials were measured.
Bottom‑up
e bottom-up method can be divided into physical
preparation, chemical preparation and other bottom-up
methods. Physical preparation includes molecular beam
epitaxy (MBE) in physical vapor deposition, and chemical
preparation includes chemical vapor deposition (CVD),
hydrothermal method and solvothermal method.
Molecular beam epitaxial
MBE is a vacuum coating technology in the synthesis of
modern semiconductor device materials. e thickness,
crystal orientation and doping amount of Xenes can be
accurately controlled by this method. For instance, using
black phosphorus as the precursor, P
4
molecules were
condensed from the vapor phase on the surface of Au
(111) substrate. After deposition and annealing, mon
-
olayer phosphorus with regular hexagonal morphology
was formed [74]. As shown in Fig.6a, high resolution
scanning tunnelling microscopy (HRSTM) showed that
the single phosphorus layer was highly ordered, and
each dark center was surrounded by six triangles. e
average distance between dark centers was about 14.7Å.
e measured electronic band gap of a single layer of
P
4
was about 1.10eV, which indicated that it was a new
kind of two-dimensional semiconductor material. It was
consistent with the theoretical predictions reported by
Zhu etal. e DFT calculations predicted the new form
of 2D phosphorus with a flat "zigzag ridge", which was
Fig. 5 a TEM image of the multilayer arsenene/InN/InAs. (Inset:diffraction pattern of multilayer arsenene). b Thetheoretical atomic model of
multilayer arsenene/InN/InAs layer structure. Reprinted with permission [69], Copyright 2016 American Chemical Society. c TEM image of the
multilayer antimonene/InN/InSb. d The theoretical atomic model of multilayer antimonene/InN/InSb layer structure.Reprinted with permission [70],
Copyright 2016 Royal Society of Chemistry
Page 9 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
similar to that of silene with layered honeycomb struc-
ture. 2D antimony was also obtained by MBE method
besides 2D phosphorus. Monolayer antimonene with
regular orientation and order array could grow on a
chemical stable layered TMD substrate (PdTe
2
) [75]. e
small mismatch (less than 2.3%) of the surface lattice
constant between the substrate (PdTe
2
, 4.01Å) and that
of free-standing antimonene (4.01Å) should be a criti
-
cal factor for the formation of the 2D antimony film. e
resultant antimony membrane with honeycomb lattices
is similar to graphene is highly ordered and symmetric.
e height of antimony coating was 2.8 Å, which was
close to the calculated height of monolayer of antimony
(3.38Å) (Fig.6b).
e large band gap of 2D monolayer antimony indi
-
cated the potential applications for electronic and pho-
toelectric devices. Silicon is identified as a suitable
alternative substrate to prepare Xenes by MBE method
[76, 77]. For example, full-wafer monocrystalline bismuth
films with the thickness within the range of 4 ~ 50 nm
have been grown on Si (111) substrates by MBE (Fig.6c)
[78]. Si (111) substrate was firstly soaked with dilute
hydrofluoric acid to remove the natural oxide and then
the substrate was loaded into a high vacuum and baked
at high temperature within 20 min to prevent second
-
ary oxidation. Bismuthene grows at a rate of 0.2Å/s at
room temperature observed by TEM. Bismuthene pos
-
sesses good 2D topological structure due to its quantum
Fig. 6 a Atomic model of blue phosphorus and experimental morphological (STM) images of phosphorus. Reprinted with permission [74],
Copyright 2016 American Chemical Society. b Monolayer antimonene formed on PdTe2 substrate, experimental morphological (TEM and AFM)
images of antimonene. Reprinted with permission [75], Copyright 2017 Wiley. c Morphological of the transferred Bi films. Reprinted with permission
[78], Copyright 2016 American Chemical Society. d Left: Topographic image (size: 100 × 100 nm2, sample bias: 1 V) of an epitaxial Te film showing
an atomically flat terraces separated by steps of height of ~ 4 Å. (The inset presents a line profile taken along the white line drawn in the image).
Right: Atomic resolution STM image (size 8 × 8 nm2, bias: 0.6 V) showing rectangular lattices as highlighted by the black rectangle. Reprinted with
permission [79], Copyright 2017 Royal Society of Chemistry
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Gaoetal. J Nanobiotechnol (2021) 19:96
size effect, low carrier density and spin coupling effect.
As for Group VIA, tellurene (2D tellurium) was recently
grown on both graphene/6H-SiC (001) and high orien
-
tation pyrolysis graphene (HOPG) using MBE technol-
ogy [79]. As shown in Fig.6d, the lattice of tellurene is
rectangular and the surface lattice constant is consistent
with the theoretical lattice constant. e tellurium thin
films feature semiconductor characters, and the band gap
decreases with the increase of thickness. MBE method
could control the growth of Xenes at atomic scale due to
the slow deposition rate, however, the difficult operation
limits their more applications.
Chemical Vapor Deposition (CVD)
CVD technology has gradually become an important
route for synthetic of uniform 2D inorganic materials.
BP thin films with an average area of above 3 μm
2
were
prepared from red phosphorus successfully with insitu
chemical vapor deposition method [80]. e film was
composed of four phosphorus atomic layers. In recent
years, many new 2D nanomaterials have been prepared
by CVD technology. e controllable growth of Sb
2
Te
3
nanosheets occurs on the surface of SiO
2
[81]. Bismuth
oxide monocrystalline films could be prepared on amor
-
phous substrates by aerogel-assisted CVD [82]. Chang
etal. used CVD technology to prepare continuous InSe
films possessing high stability against oxidation [83].
CVD technology has many advantages in the prepara
-
tion of two-dimensional materials. e deposition rate
can be controlled by adjusting the process parameters,
such as gas pressure, gas velocity, temperature rising rate
and heat preservation time. CVD technology is simple
and relatively low in cost, which is suitable for large-scale
production and wide applications [84, 85].
Solvent‑thermal method
Solvent-thermal method is a common method to syn-
thesize nanomaterials. An impressive body of literature
indicates that solvent-thermal approach is a reliable
method for the synthesis of BP nanosheets. For instance,
high yield of BP nanosheets (30%) was prepared at 400
(Fig. 7a) [86]. After vacuum drying, the uniform
2D nanocrystals with the transverse size of 1 μm and
the thickness of 0.5–4 nm were obtained, which was
characterized by less than 8 layers of black phosphorus
atoms (Fig. 7b–d). e lattice fringes of 0.27 nm and
0.23nm were on the (040) and (002) planes of orthogo
-
nal BP. e resultant BP nanosheets feature excellent
electrochemical properties as the positive electrode of
lithium ion battery. Tian etal. [87] took white phospho
-
rus as raw material and ethylenediamine as solvent to
obtain BP nanosheets with a few atomic layers through
solvent-thermal approach (Fig.7e–h). More interestingly,
the higher the solvothermal reaction temperature (in
60–140 range), the higher the yield of BP production.
e thickness of the synthetic BP nanosheets was within
the scope of 1–15 nm, which was comprised of 2–28
atomic layers. It was conducive to the expansion of BP
application scope in the field of optoelectronic devices.
As for tellurium, sodium tellurite (Na
2
TeO
3
) is a
common tellurium source with hydrazine hydrate
(N
2
H
4
•H
2
O) as the reducing agent for the preparation
of 2D tellurium by solvent-thermal approach [88]. As
shown in Fig.7i–k, the measurements of TEM and AFM
consistently demonstrated that the uniform dimensions
(about 15 μm) with the thickness of 10–30 nm of tel
-
lurene can be achieved by this process. e result indi-
cated that Te nanosheets were continuous lattices with a
lattice constant of 2Å corresponding to the (003) plane
of Te. Moreover, the thickness of 2D tellurium nanocrys
-
tals could be adjusted from single molecule membrane to
10nm by controlling reaction conditions. e resultant
2D tellurium nanosheets have high stability. In conclu
-
sion, the yield and morphology of 2D nanocrystals are
dramatically influenced by reaction temperature, raw
materials, solvents, and surfactants in this process.
Other bottom‑up methods
In order to obtain 2D materials with high crystallinity by
CVD technology, the perfect match in symmetry and lat
-
tice constants between the epitaxial layer and substrate is
a key index. Van der Waals epitaxy technology is recently
proposed to seed the epitaxial growth of 2D materials
on the substrate without suspended bond to avoid the
above restrictions. Ten atomic layered antimonene was
obtained by van der Waals epitaxy from antimony poly
-
hedrons on a bare (001) plane fluorochemical substrate
(KMg
3
(AlSi
3
O
10
)F
2
). e antimony vapor in the heat was
Figure7 a The morphology evolution of the bulk red phosphorus materials during the high-temperature solvothermal reaction. b
Low-magnification of TEM images of the holey phosphorus-based nanosheets. Reprinted with permission [86], Copyright 2016 Wiley. c HRTEM
image of phosphorus-based nanosheets, showing the amorphous regions with some polycrystalline structure. d AFM image. e Synthetic protocol
of the black phosphorus. f TEM image of the BP nanosheets. g HRTEM image corresponding to F. Lattice Image of a BP flake shows d spacing of the
(020) plane of orthorhombic BP. h AFM image. Reprinted with permission [87], Copyright 2018 PNAS. i TEM images of the tellurium nanoflakes. j
Corresponding HR-TEM image. k AFM image of typical tellurium nanoflake (top) and the corresponding height profile (bottom), scale bar is 1 µm.
Reprinted with permission [88], Copyright 2018 American Chemical Society
(See figure on next page.)
Page 11 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Page 12 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
transported downstream with Ar/H
2
mixed gas result-
ing in thin antimonene films with less than 4nm [89].
Wet chemistry is another common bottom-up method
to prepare Xenes. Bismuthene was synthesized by this
method. e black sediment was obtained from the mix
-
ture of Bi(NO)
3
·5H
2
O, added water, ethylene glycol and
hydrazine hydrate (volume ratio 6:3:1) under vigorous
stirring it at 80 for 8h [90]. More recently, Zhao etal.
[91] deposited ultrathin tellurium films by thermal evap
-
oration at low temperature (80) when the pressure
reached 2 × 10
–6
mbar. Tellurium thin film prepared by
this method has high Hall mobility and is a kind of high
performance p-type field effect transistors (FET) mate
-
rials with good switching characteristics. It has a broad
application prospect in electronic devices and mono
-
lithic 3D circuits. Tan etal. also reported the use of low
temperature (110°C) thermal evaporation to prepare
Se
x
Te
1-x
thin films with continuous adjustable band gap
from 0.31eV (Te) to 1.87eV (Se) [92]. e films have
great application potential in the manufacture of low
cost, high performance, high resolution short-wave infra
-
red (SWIR) photodetectors and imaging sensors.
Application ofXenes inbiomedicine
erapeutic applications of 2D Xenes have witnessed
rapid growth for biomedical applications in recent
years. Because of their outstanding physical, chemical,
electronic and optical properties, 2D Xenes have been
explored in a variety of biomedical applications, such as
bioimaging, photothermal therapy (PTT), photodynamic
therapy (PDT), chemotherapy and antibacterial. ese
various adopted strategies in biomedical applications are
described as follows.
Bioimaging
Multimode imaging is paramount importance for the
identification and diagnosis of the disease. It is a routine
technique to visualize morphological details in cells and
tissues to avoid unnecessary biopsies and reduce patient
suffering [93]. In this section, we will discuss the applica
-
tions of 2D Xenes in fluorescence imaging (FI), photoa-
coustic imaging (PAI), and X-ray computed tomography
(CT) imaging.
FI is the visualization of fluorescent dyes or proteins as
labels for molecular processes or structures. FI is a com
-
mon biological imaging model to achieve observations
including the location and dynamics of gene or protein
expression and molecular interactions in cells and tis
-
sues. 2D Xenes with ultra-high specific surface area can
efficiently load fluorescent dyes for fluorescence imag
-
ing. BP has been widely demonstrated as an excellent
fluorescent dye delivery platform to achieve the require
-
ment of real-time imaging for living tissue. For example,
the modified nile blue dye (NB) was covalently modi
-
fied BP nanosheets to form NB@BP, which could label
MCF-7 tumor sites with red fluorescence and achieve
effective tumor ablation under near-infrared irradiation
(Fig.8a) [94]. Fluoresce in isothiocyanate (FITC)-labelled
PEG-BP NSs has been demonstrated that it could enter
HeLa cells through cavity-dependent endocytosis and
macroendocytosis [95]. is result provides an available
evidence for deep investigating the transport mecha
-
nism and distribution of BP in cells. PEGylated BP load-
ing Cy7 could achieve a good accumulation in the tumor
sites model resulting invivo imaging [21]. BP quantum
dots have good biocompatibility, low toxicity, spontane
-
ous degradation analogous to BP nanosheets, especially
intrinsic fluorescence properties making it a broad appli
-
cation prospect in bioimaging. Lee etal. found that black
phosphor quantum dots emitted blue fluorescence in
HeLa cells under UV irradiation and green fluorescence
under visible light irradiation (Fig.8a) [96]. Additionally,
antimonene has also been explored in fluorescence imag
-
ing field showing good accumulation and retention in the
mouse model of breast cancer cell inoculation (Fig.8b)
[27]. Cy5.5-labeled PEGylated antimonene nanosheets
were absorbed into MCF-7 cells by mass endocytosis and
cave-independent endocytosis, and then transported by
early endocyt-late endocyt-lysosome pathway.
PAI, which is based on the photoacoustic effect, is an
emerging diagnostic modality to achieve the detection
of laser-irradiated tissue-induced pressure waves. PAI
has been applied to the imaging of cancer, wound heal
-
ing, disorders in the brain, and gene expression, among
others. Due to the thickness-dependent quantum size
effect and adjustable crystal structure of Xenes, it is an
extremely attractive PAI reagent to achieve the sectional
or three-dimensional images of tissues and organs. For
example, PEGylated BP nanosheets have been demon
-
strated as a good PAI agent [97]. As shown in the Fig.8c,
PAI signal was enhanced with the increase of concentra
-
tion of PEGylated BP nanosheets. PA signals in tumor
sites were strong for several hours following the injection
of PEGylated BP nanosheets, indicating the low tissue-
attenuation coefficient and the prominent accumulation
in tumor focus in comparison with the other organs. In
addition to BP, Tao et al. have developed the uniform
antimonene nanosheets and successfully applied it as PAI
agents in bioimaging [27]. ey reported that the PAI
signal of antimonene nanosheets was stronger than that
of BP nanosheets, which was more suitable for invitro
and in vivo imaging. Recently, other forms of Xenes
including ultrasmall bismuth [98] (2D Bi) nanoparticles
and tellurene [99] (2D Te) nanosheets were also reported
to be ideal candidate for the application in PAI.
Page 13 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Fig. 8 Emerging Xene-based bioimaging. a NB@BP-based fluorescence imaging (FL) and BP quantum dots based fluorescence imaging
(FL). Reprinted with permission [94], Copyright 2017 American Chemical Society. Reprinted with permission [96], Copyright 2016 Wiley. b
Antimonene-based fluorescence imaging (FL) and photoacoustic imaging (PAI). Reprinted with permission [27], Copyright2018 Wiley. c) BP-based
photoacoustic imaging (PAI). Reprinted with permission [97], Copyright 2016 Elsevier. d Bismuthene-based X-ray computed tomography (CT)
imaging. Reprinted with permission [101], Copyright 2017 Wiley
Page 14 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Combining with special computer-aided X-ray technol-
ogy, CT utilizes ionizing radiation to provide 3D images
of biological tissues and fine cross-sections with high
resolution and deep penetration noninvasively. Given
the advantages of long half-life, easy modification and
specific enrichment in tumor region, Xene-based nano
-
materials also have great potential in the application of
CT imaging. Bismuth possesses good X-ray attenuation
performance, which is relatively cheaper and lower toxic
compared with the conventional CT agents. e edge
value of bismuth (K = 90.5 keV) is three times greater
than that of iodine-based medicine (K = 33.2keV), which
is a common clinic CT agent. erefore, bismuth-based
nanomaterials could maximize the X-ray absorption
efficiency and have good CT imaging potential [100].
Lei et al. synthesized ultra-small PVP-coated Bi nano
-
dots and demonstrated the improved CT imaging results
[101]. e CT imaging resolution is triple as high as that
of the traditional iodine-based contrast agent (Fig.8d).
Liu etal. prepared Bi@Gel (BGPS) and proved that CT
signal was enhanced with the increase of BGPS concen
-
tration [102]. e Hounsfield unit slope of BGPS is 6.464
Humm
1
, higher than that of iohexol (4.28 HumM
1
)
resulting in excellent CT imaging. e obvious CT sig
-
nals could be detected at the tumor site after injection
for 24h, which further proved that the CT imaging per
-
formance of BGPS effectively accumulated in the lesion.
In this context, Xene-based nanomaterials are widely
considered as a potential alternative invitro and invivo
imaging. Furthermore, combining these diverse imaging
methods could improve the spatial and temporary sensi
-
tivity of imaging systems for tumor therapy.
Therapeutic applications
e treatment of the disease, especially targeted therapy,
is essential inclinical medicine [103106]. Chemotherapy,
photothermal therapy (PTT) and photodynamic therapy
(PDT) are the most common therapeutic methods based
on Xene nanostructures.
PTT is a physical treatment approach to destruct can
-
cer using local hyperthermia generated by photother-
mal agent with high photothermal conversion efficiency.
Xenes with strong absorption in the region of near-
infrared light, has been widely used as photothermal
agents for PTT due to their unique optical performance
[22]. For example, the fatality rate of BP-PEG nanosheets
under 1W/cm
2
laser irradiation on HeLa cells reached
90%, indicating that BP-PEG nanosheets can promote the
death of cancer cells by good photothermal effect. Invivo
experiments showed that BP-PEG could enhance the
anti-tumor effect through the combination of PTT and
chemotherapy, and no tissue damage was found in the
main organs. Additionally, the photothermal conversion
efficiency of Ce6-modified BP nanosheets were reported
as high as 43.6%. Apart from BP in group VA, 2D anti
-
mony quantum dots (AM QDs) have been prepared and
functionalized by PEG. e temperature of PEG-coated
AMQDs could increase up to 50 at the concentra
-
tion of 200μg/mL, indicating the extremely high pho-
tothermal conversion rate (45.5%). More importantly,
PEG-coated AM QDs could degrade rapidly under the
action of near-infrared light after executing PTT against
tumor. And invivo experiment against MCF-7 indicates
that 2D AM QDs have the best antitumor effect with
-
out recurrence and obvious side effects induced by local
hyperthermia (Fig. 9a) [26]. It was reported that PVP
encapsulated Bi QDs (PVP-Bi QDs) also exhibited good
photothermal conversion capability under laser irradia
-
tion of 808nm at the power of 1.3 w/cm
2
. e temper-
ature of PVP-Bi QDs sharply rose up to 49.5 within a
short time, indicating PVP-Bi QDs could rapidly convert
near-infrared light into heat energy. e measured pho
-
tothermal conversion efficiency was about 30%. After
treating U14 tumor with PVP-Bi quantum dots combined
with laser irradiation, the cytotoxicity and effects on nor
-
mal cells were negligible (Fig. 9b) [102]. As for Group
VIA, Te-based nanomaterials have been proposed to per
-
form PTT to achieve the purpose of tumor ablation. Yang
and co-workers presented the synthesis of bifunctional
tellurium nanodots, which could not only achieve effec
-
tive photothermal transformation but also generate ROS
to mediate apoptosis in tumor cells (Fig.9c) [107].
PDT is nowadays another form of phototherapy to
destruct cancer, which possesses the therapeutic proce
-
dure exerting a selective cytotoxic activity toward malig-
nant cells. In the presence of oxygen, the photosensitizer
or photosensitizing drug could produce reactive oxygen
species (ROS) by irradiation at a certain wavelength cor
-
responding to an absorbance band of the sensitizer. e
irreversible oxidative damage to the cancer cells in malig
-
nant tissues is induced by the generated ROS and there
is the minimal normal tissue toxicity. Clinical studies
Fig. 9 Emerging Xene-based therapeutic applications. a Antimonene-based photothermal therapy (PTT). Reprinted with permission [26],
Copyright 2017 Wiley. b Bismuth-based photothermal therapy (PTT). Reprinted with permission [101], Copyright 2017 Wiley. c Tellurium
Nanodots-based photothermal therapy (PTT) and Photodynamic therapy (PDT) Reprinted with permission [22], Copyright 2017 American Chemical
Society. d, e Black phosphorous-based Photodynamic therapy (PDT). Reprinted with permission [107], Copyright 2015American Chemical Society. f,
g Tellurene-based photodynamic therapy (PDT). Reprinted with permission [109], Copyright 2018 Royal Society of Chemistry
(See figure on next page.)
Page 15 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Page 16 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
have shown that PDT can be curative and significantly
improve the reduction of recurrence risk, particularly in
early stage tumors. Various advantages make it a valuable
therapeutic schedule for combination treatments.
Fortunately, Xene-based photosensitizers are expected
to overcome the forementioned limitations. Xene itself
is not only an ideal candidate for PDT but also can
be loaded with photosensitizing drug due to its super
high specific surface area. Wang etal. reported that BP
nanosheets produced singlet oxygen under 660nm laser
irradiation at the power of 1W/cm
2
to induce apoptosis
of tumor cells, and the apoptosis rate was 71.5% [108]. As
shown in Fig.9d, e, both invitro and invivo experimen
-
tal results indicated that the BP nanosheets have great
potential for using as a photosensitizer. Numerous stud
-
ies show that the synergistic effect of PTT and PDT can
effectively inhibit tumor growth. Yang etal. constructed
a dual functional Ce6-modified BP nanosheets to real
-
ize PDT/PTT synergistic treatment [109]. is combi-
nation was endowed with good biocompatibility and
obvious synergistic effect. It was also less-invasive for
normal cells, heart, liver, spleen, kidney and other major
organs. Lin etal. prepared glutathione coated tellurium
nanosheets (Te@GSH), which showed a noteworthy PDT
capability with a high quantum yield about 0.91 of singlet
oxygen (
1
O
2
) under 670nm light irradiation (Fig.9f, g)
[98]. Te@GSH could produce
1
O
2
and effectively inhibit
the growth of tumor cells. Hematoxylin–eosin (H&E)
staining images showed that the tumor sections in the
Te@GSH light group were seriously damaged, while the
morphology of other cells was normal and the physi
-
ological morphology of the viscera was not changed. Te@
GSH was further proved a safe and reliable PDT agent.
In addition to the two-dimensional Xenes materials men
-
tioned above, the applications of BP QDs and tellurium
nanoparticles in PDT have also been reported.
Although there are some drawbacks, chemotherapy
is still the main method for cancer therapy in clinical
present. e satisfying chemotherapy effect could be
achieved via combining 2D Xenes with anticancer func
-
tional drug. 2D Xenes have unique lamellar structure,
adjustable atomic layer thickness, large specific surface
area and easy surface functionalization. ese advantages
provide an important basis for high drug loading and
effective drug delivery [28, 110]. As a newly developed
2D material, BP nanosheets are metal-free layered semi
-
conductors with variable band gap, high surface reactiv-
ity, strong biodegradability, large specific surface area,
which can efficiently load drug molecules, antibodies
and biological molecules. erefore, combining anticar
-
cinogen with BP nanosheets is an effective approach for
chemotherapy. For example, Chen and co-workers pre
-
sented the synthesis of a multifunctional system, which
combined BP nanosheets and lipophilic drugs (doxo
-
rubicin, DOX) through electrostatic effect (Fig. 10a, b)
[111]. e loading capacity of DOX reached up to 950%,
which was much higher than the drug loading of con
-
ventional deliveries reported previously. More impor-
tantly, the release rate of the drug at pH 5 was 6 times
higher than that at pH 7, demonstrating that the drug
was beneficial to release at a lower pH and the release
profile was pH-dependent. Because of the acidic tumor
microenvironment, BP-DOX is favorable for drug release
within the tumor. BP has photothermal effect, which can
further promote the release of DOX. Under the irradia
-
tion of 808nm laser, the release rate of DOX was up to
90%. In addition to DOX, chloroquine (CQ) has also
been successfully loaded onto BP nanosheets [112]. e
BP nanosheets loaded with CQ enter the cell lysosomes,
realizing the synergistic treatment of photothermal ther
-
apy and chemotherapy, which significantly improved
the therapeutic effect of cancer. Following these studies,
Zeng group employed polydopamine (PDA) to inno
-
vate a facile and low-cost surface modification strat-
egy to endow BP nanosheets with good water-solubility
and bio-compatibility (Fig.10c, d) [113]. DOX and P-gp
siRNA physically adsorbed on the surface of PDA coated
BP-based drug delivery for multidrug resistant cancer
treatment. e release rate of DOX and P-gp siRNA
could be effectively controlled by adjusting pH and near
infrared laser irradiation. In vivo experiments showed
that the system could successfully introduce drugs into
tumor cells, and exhibited a significant synergistic ther
-
apeutic effect on multidrug resistant breast cancer. In a
word, by constructing a PDA-modified BP nanosheets
multifunctional drug delivery platform, the water-solu
-
bility, bio-compatibility and photothermal performance
could be improved. It could not only achieve selective cell
targeting, but also show effective inhibition of tumor cell
proliferation through multi-mode combination therapy.
e multifunctional drug delivery system provides
a new direction for targeted chemotherapy and gene
therapy for multidrug resistant cancers. Tao et al. has
reported the coating of antimony nanosheets (2D Sb)
multifunctional system with amphiphilic PEG polymer
for targeted delivery of chemotherapy drugs and photo
-
thermal therapy [27]. As illustrated in Fig.10e, f, anti-
mony nanosheets were encapsulated by PEG grafted
amphiphilic polymer to offer a "hydrophobic arm" with
the feasibility of physically absorbance "catching" lipo
-
philic drugs (DOX) by hydrophobic interaction. e
obtained drug loading capacity was about 150% (weight
ratio) and the measured drug release rate was 69.8%
at pH 5 under the near-infrared irradiation. AM-PEG/
DOX has deep photoinduced penetration and excellent
photothermal conversion capability. e apoptosis rate
Page 17 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
of MCF-7 cells was about 91.5% and the tumor growth
inhibition rate (TGI) of this strategy reached 98.1%,
which was significantly higher than that of monotherapy.
It was the first time to report the photon drug delivery
platform of 2D Sb nanosheets, which may indicate a new
starting point in cancer treatment research. Apparently,
Fig. 10 a, b Phosphorene-based drug delivery systems. Reprinted with permission [28], Copyright 2017 Wiley. c, d Polydopamine-modified black
phosphorous-based drug delivery systems Reprinted with permission [112], Copyright 2019 Wiley. e, f Antimonene-based drug delivery systems.
Reprinted with permission [27], Copyright 2018 Wiley
Page 18 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Xenes as drug delivery have attracted extensive attention
and made rapid progress in research. Although there are
still huge challenges, it is believed that in the near future,
Xenes will make great breakthroughs and realize clinical
applications.
Antibacterial
Bacterial infection is a process in which bacteria invade
and cause local or systemic damage to the host, thus
showing its pathogenicity and inducing the occurrence
of disease. Currently, the most common treatment for
bacterial infections is antibiotic therapy. However, due
to the emergence of multi-drug resistant superbugs, tra
-
ditional antibiotics are no longer able to solve the arisen
problem of bacterial infection. An overuse of antibiotics
has further accelerated the creation of antibiotic-resist
-
ant germs [114, 115]. To date, tremendous efforts have
been devoted to settle the awful bacterial drug resist
-
ance. Xenes have good membrane permeability, excel-
lent biocompatibility, large specific surface area and easy
surface modification, so they can interact with bacterial
membranes better and improve antibacterial effect dis
-
tinctly. At present, great progress has been made in the
development of Xenes based antibacterial agents [29, 30].
For instance, Sun etal. employed BP nanosheets as an
antibacterial agent to against gram-negative escherichia
coli (E. coli) and gram-positive staphylococcus aureus (S.
aureas) by means of 808nm irradiation [116]. e steri
-
lization rate was as high as 99.2%, far higher than that of
graphene and 2D MoS
2
, showing significant antibacterial
ability (Fig.11a). e effect of BP nanosheets on staphy
-
lococcus aureus were slightly larger than that of E.coli,
which may be related to the different microstructure of
different cell wall. Within a certain concentration range,
the bacterial lethality improved and the cytotoxicity
would be negligible with the increasing of BP concentra
-
tion, indicating the good biocompatibility and the great
potential in antibiotic area. Ouyang’ group constructed
a novel Ag@BP nanostructure on the substrate of BP
nanosheets [117]. Under near-infrared light, BP substrate
has excellent photothermal effect and can rapidly destroy
bacterial membrane. Synergistically Ag
+
was released
slowly by oxidative dissolution mechanism to inhibit the
proliferation of bacteria. ey demonstrated that higher
amounts of methicillin-resistant staphylococcus aureus
(MRSA) death (93%) caused by Ag@BP than BP alone.
After treatment with Ag@BP, the skin tissue was intact
and the inflammation was effectively inhibited. e anti
-
bacterial effect of Ag@BP is mediated by local high tem-
perature and oxidative stress, and has nothing to do with
the structure of bacteria, thus avoiding the occurrence of
drug-resistant bacteria. Ag@BP have good biocompat
-
ibility and biosafety making them have great potential
in clinical application in the future. is work also laid
a foundation for the treatment of drug-resistant bacte
-
ria based on two-dimensional semiconductor and other
antibacterial material microspheres. Zhang etal. directly
synthesized a new type of copper-carrying (BP/Cu) nano
-
composite by one-step reduction method, and studied its
antibacterial mechanism (Fig.11b–f) [118]. Active lone
pair electrons could allodially transfer from BP to the sur
-
face of metal according to the invivo experiments. e
interaction between BP and copper leads to the increase
of ROS production mainly including hydroxyl radicals
and superoxide anion. e generated ROS active species
could directly damage the cell membrane, phospholipid
or membrane protein, thereby destroying the bacterial
structure and further inducing bacterial death.
In addition to BP, antimony nanosheets have great
potential for synergistic antibacterial applications. Liu
etal. introduced antimony nanosheets into the center
of chitosan (CS) network to construct a composite
hydrogel (CS/AM-NSs hydrogel) with excellent anti
-
bacterial properties (Fig.11g–i) [119]. e interaction
between CS and bacterial membrane made the bacte
-
ria accumulate on the surface of the composite hydro-
gel. e bactericidal property of the composite could
kill most bacteria, and the photothermal properties of
the antimony nanosheets could eliminate the residual
bacteria. e antibacterial test results invitro showed
that the killing rate of CS/AM-NSS0.8 hydrogel against
E.coli and S. aureus was 97.1% and 100%, respectively.
e results showed that the synergistic effect of CS,
AM-NSs and PTT could effectively kill bacteria and
further promote wound healing. ere was no obvi
-
ous inflammation, injury or necrosis, no aggregation of
materials in major tissues and organs, and the toxicity
was relatively weak in vivo. e material is expected
to be widely used in bandages to treat bacterial wound
infections. 2D antimony based nanomaterials was used
in antimicrobial therapy for the first time, providing
a future direction of biomedical applications for 2D
Fig. 11 Emerging Xene-based antimicrobial application. a Phosphorene-based antimicrobial application. Reprinted with permission [115],
Copyright 2018 Royal Society of Chemistry. bf BP loaded copper (BP/Cu)-based antimicrobial application. Reprinted with Reprinted with
permission [116]. Copyright 2020 Elsevier. g Schematic illustration of the preparation of CS/AM NSs hydrogel and its use in treating bacterial wound
infection. h, i Pictures of antibacterial effect in vitro and photographic images and tissue sections of wounds treated by Staphylococcus aureus
infection. Reprinted with permission [117], Copyright 2020 Wiley
(See figure on next page.)
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Gaoetal. J Nanobiotechnol (2021) 19:96
Page 20 of 23
Gaoetal. J Nanobiotechnol (2021) 19:96
Xenes. Rangrazi et al. synthesized chitosan groomed
selenium nanoparticles (CTS-Se NPs) directly by a sim
-
ple chemical reduction method with ascorbic acid as
reducing agent [120]. e results showed that CTS-Se
NPs exhibited obvious bactericidal effect on gram-pos
-
itive bacteria, streptococcus sanguis, staphylococcus
aureus and enterococcus faecalis even at extremely
low concentration of CTS-Se NPs. Moreover, this sys
-
tem had no obvious inhibitory effect on gram-positive
pseudomonas aeruginosa and salmonella typhimurium,
which indicated that it possessed selective antibacterial
function. CTS-Se NPs have great reference and applica
-
tion value in medical field such as forehead sterilization
of medical devices and mouthwash for dental diseases.
In brief, 2D Xenes are conducive to contact with bac
-
teria and penetrate the cell membrane due to their
internal features containing high specific surface area,
light-induced ROS production, outstanding photother
-
mal conversion efficiency.
Conclusion andprospect
In this review, we summarized the recent developments
in 2D Xenes (group VA and group VIA) in terms of
design, synthesis and biomedical applications. Numer
-
ous typical examples were enumerated to demonstrate
the various aspects of 2D Xenes in detail. Admittedly,
the research of 2D Xenes has made substantial advances
in recent years, however, several technical challenges
remain, which impose barriers to their practical appli
-
cations. On one hand, controllable preparation of 2D
Xenes is of primary importance, including morphology,
composition and adjustable surface properties. ere is
no standard method to synthesize 2D Xenes and how to
prepare 2D Xenes on a large scale is still a huge challenge.
erefore, more profound understanding still needs to be
explored in future. On another hand, an urgent task is to
pinpoint the biosecurity of 2D Xenes including the accu
-
mulation, the accurate retention time in the lesion and
the actual clearance mechanism. 2D Xenes are ingested,
the prognosis within the body and the generated effect
on nervous and immune system still needs to be further
systematic studied. erefore, further nanotoxicology
and pharmacokinetics studies on 2D Xene-based thera
-
nostic platform should be carefully confirmed.
In conclusion, 2D Xenes are facing unprecedented
challenges and opportunities in biomedical fields. e
realization of theoretical knowledge and clinical appli
-
cations of 2D Xenes nanomaterials requires the joint
efforts of all researchers. It is believed that with the con
-
tinuous development of nanotechnology, 2D Xenes will
be applied in a variety of biomedical fields in the near
future.
Abbreviations
2D: Two-dimensional; Xenes: Monoelemental nanomaterials; TMD: Transition
metal dihalide; h-BN: Hexagonal boron nitride; g-C
3
N
4
: Graphite phase nitro-
gen carbide; MoS
2
: Molybdenum disulfide; LRH: Layered rare earth hydroxide;
LDH: Layered double hydride; CT: Computed tomography; PAI: Photoacoustic
imaging; FI: Fluorescence imaging; PTT: Photothermal therapy; PDT: Photo-
dynamic therapy; TEM: Transmission electron microscopy; AFM: Atomic force
microscope; CHP: N-cyclohexyl-2-pyrrolidone; DMF: Dimethylformamide;
DMSO: Dimethylsulfoxide; IPA: Isopropyl alcohol; NMP: N-methyl-pyrrolidone;
QDs: Quantum dots; DSPE-mPEG: 1,2-Distearoyl-sn-glycero-3-phosphoethan-
olamine-N-[methoxy (poly ethylene glycol)]; NH
4
PF
4
: Ammonium hexafluoro-
phosphate; MBE: Molecular beam epitaxy; CVD: Chemical vapor deposition;
HRSTM: High resolution scanning tunneling microscopy; Na
2
TeO
3
: Sodium
tellurite; N
2
H
4
·H
2
O: Hydrazine hydrate; NB: Nile blue; FITC: Fluoresce in isothio-
cyanate; ROS: Reactive oxygen species; Te@GSH: Glutathione coated tellurium
nanosheets; H&E: Hematoxylin–eosin; TGI: Tumor growth inhibition rate; E. coli:
Escherichia coli; S. aureas: Staphylococcus aureus; MRSA: Methicillin-resistant
staphylococcus aureus; CS: Chitosan.
Authors’ contributions
PG and YX wrote the main draft under LL and WLs supervision. YW helped in
paper writing, WT helped in final editing. All authors read and approved the
final manuscript.
Funding
Financial support by National Natural Science Foundation of China (No.
21871246; to LL), the Grant of Jilin Province Science & Technology Committee
(No. 20180101194JC and 20200201082JC; to LL and WL), the Science & Tech-
nology Innovation and Development projects of Jilin city (No. 20190601178;
to WL), Jilin Province Education Department the Science & Technology
development project (No. JJKH20200741KJ and JJKH20200449KJ; to LL and
WL) are acknowledged.
Availability of data and materials
Not applicable.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
School of Chemistry and Environmental Engineering, Changchun University
of Science and Technology, Changchun 130022, China.
2
Center for Nanomed-
icine and Department of Anesthesiology, Brigham and Women’s Hospital, Har-
vard Medical School, Boston, MA 02115, USA.
3
Jilin Collaborative Innovation
Center for Antibody Engineering, Jilin Medical University, Jilin 132013, China.
Received: 15 January 2021 Accepted: 6 March 2021
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